Development and in-vivo characterization of supramolecular hydrogels for intrarenal drug delivery.

Intrarenal drug delivery from a hydrogel carrier implanted under the kidney capsule is an innovative way to induce kidney tissue regeneration and/or prevent kidney inflammation or fibrosis. We report here on the development of supramolecular hydrogels for this application. We have synthesized two types of supramolecular hydrogelators by connecting the hydrogen bonding moieties to poly(ethylene glycols) in two different ways in order to obtain hydrogels with different physico-chemical properties. Chain-extended hydrogelators containing hydrogen bonding units in the main chain, and bifunctional hydrogelators end-functionalized with hydrogen bonding moieties, were made. The influence of these hydrogels on the renal cortex when implanted under the kidney capsule was studied. The overall tissue response to these hydrogels was found to be mild, and minimal damage to the cortex was observed, using the infiltration of macrophages, formation of myofibroblasts, and the deposition of collagen III as relevant read-out parameters. Differences in tissue response to these hydrogels could be related to the different physico-chemical properties of the three hydrogels. The strong, flexible and slow eroding chain-extended hydrogels are proposed to be suitable for long-term intrarenal delivery of organic drugs, while the weaker, soft and fast eroding bifunctional hydrogel is eminently suitable for short-term, fast delivery of protein drugs to the kidney cortex. The favourable biological behaviour of the supramolecular hydrogels makes them exquisite candidates for subcapsular drug delivery, and paves the way to various opportunities for intrarenal therapy.